Vascular permeability factor (VPF)-vascular endothelial growth factor (VEGF), has been proposed to be a mediator of endothelial proliferation and angiogenesis in normal and diseased states, and to have a role in the development of tumor-associated vascular hyperpermeability. VEGF-VPF exists as multiple forms due to alternative splicing of the gene, and these forms exhibit different biologic behaviors. We have determined that the expression of these multiple forms is organ-specific, suggesting that the functions of VEGF/VPF are organ-specific as well. In tissue culture cells hypoxia (<12% oxygen) is a potent inducer of VEGF/VPF gene expression. This may be part of the mechanism involved in hypoxia- induced cerebral angiogenesis and in ischemia-induced hyperpermeability. A nonreplicating adenovirus which carries the VEGF/VPF gene is capable of infecting multiple cell types, expressing functional VEGF/VPF protein, and stimulating angiogenesis and permeability in bioassays. This construct provides a useful tool for studying the effects of VEGF/VPF in normal brain, as well as the possibility of gene therapy for cerebral ischemia. Antibody studies demonstrate that VEGF-VPF is responsible for about 75% of the permeability inducing activity produced by brain tumor cells. Hyperpermeability associated with brain tumors is a significant cause of morbidity and mortality in this disease. Steroids are the standard treatment for this condition, but the mechanism of this steroid effect is poorly understood. We have determined using a brain tumor model that this inhibition of tumor capillary permeability by steroids is mediated through the glucocorticoid receptor, a finding that has important implications for the proper clinical management of brain tumor patients.